E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that Symbicort Turbuhaler 160/4.5 μg ‘as needed’ is superior to terbutaline Turbuhaler 0.4 mg ‘as needed’. |
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E.2.2 | Secondary objectives of the trial |
1.To evaluate the relative efficacy of Symbicort Turbuhaler 160/4.5 μg ‘as needed’ and Pulmicort Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.
2.To evaluate the efficacy of Symbicort Turbuhaler 160/4.5 μg as compared to both:
terbutaline Turbuhaler 0.4 mg ‘as needed’
And:
Pulmicort Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Provision of informed consent prior to any study specific procedures. For patients under-age, signed informed consent from both the patient and the patient’s parent/legal guardian is required
2.Outpatients of either gender aged ≥12 years at Visit 1
3.Diagnosis of asthma according to GINA criteria with a documented history of at least 6 months prior to Visit 1
4.Patients who are in need for GINA step 2 treatment:
-uncontrolled on SABA ‘as needed’ as judged by the investigator for the last 30 days before Visit 2, or
-controlled on mono-maintenance therapy with low stable dose ICS (≤ 400 μg budesonide per day or corresponding dose of other ICS, or LTRAs as judged by the investigator for the last 30 days prior to Visit 2
5.Based on lung function tests at Visit 2, patients pre-treated with
-a SABA only should have prebronchodilator FEV1 ≥ 60 % of predicted normal (PN) and postbronchodilator FEV1 ≥ 80 % PN according to the European Respiratory Society (ERS) guidelines
-low dose ICS or LTRAs medication should have prebronchodilator FEV1 ≥80 % PN according to the ERS guidelines
6.Reversible airway obstruction according to a reversibility test performed at Visit 2 defined as an increase in FEV1 ≥12% and 200 ml relative to baseline, 15-30 minutes after inhalation of 1 mg Bricanyl Turbuhaler. The test can be repeated at Visit 3 in case the patients fail at Visit 2. If patients on low dose ICS or LTRAs fail at both occasions, they can still be included if they have a documented historical reversibility within the last 12 months prior to Visit 3, with an increase in FEV1 ≥12% and 200 ml relative to baseline after administration of a rapid acting β2-agonist.
For randomisation at Visit 3, patients should fulfil the following criteria:
7.Use of Bricanyl Turbuhaler ‘as needed’ due to asthma symptoms on at least 3 separate days during the last week of the run-in period.
8.Ability to use Turbuhaler correctly and to complete the eDiary correctly. Morning and evening data must be recorded for at least 8 days (any 8) of the last 10 days of the run-in period.
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E.4 | Principal exclusion criteria |
1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2.Previous enrolment in the present study
3.Participation in another clinical study with a non-biologic investigational product or new formulation of a marketed non-biologic drug during the last 30 days prior to Visit 1
4.Participation in another clinical trial with any marketed or investigational biologic within 4 months or 5 half-lives whichever is longer, prior to Visit 1
5.Any asthma worsening requiring change in asthma treatment other than SABA within 30 days prior to Visit 1
6.Use of oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1
7.Use of any β-blocking agent including eye-drops
8.Known or suspected hypersensitivity to study drugs or excipient
9.Current or previous smoker with a smoking history of ≥ 10 pack years
10.Medical history of life- threatening asthma including intubation and intensive care unit submission
11.Any significant disease or disorder (eg, cardiovascular, pulmonary other than asthma, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient’s ability to participate in the study.
12.Any clinically relevant abnormal findings in physical examination and/or vital signs at Visit 2, which, in the opinion of the investigator, may put the patient at risk if participating in the study
13.Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator
14.Planned hospitalisation during the study
15.Suspected poor capability, as judged by the investigator, of following instructions of the study.
For randomisation at Visit 3, patients should not fulfil any of the following criteria:
16.Use of ≥ 6 Bricanyl Turbuhaler ‘as needed’ inhalations per day on more than 2 days during the run-in period
17.Any asthma worsening requiring change in treatment other than SABA from Visit 1 until randomization
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of asthma control as measured by well-controlled asthma weeks as the primary variable |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
well-controlled asthma weeks, weekly, up to 52 weeks |
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E.5.2 | Secondary end point(s) |
Time to first severe asthma exacerbation
Time to first moderate or severe asthma exacerbation
Average change from baseline in pre-dose FEV1
Average change from baseline in Morning PEF
Average change from baseline in Evening PEF
Average change from baseline in number of inhalations of ‘as needed’ medication
Average change from baseline in symptom score
Percentage of Nighttime awakenings due to asthma
Percentage of Symptom-free days
Percentage of ‘As needed’ free days
Percentage of Asthma control days
Time to asthma related discontinuation
Poorly controlled asthma weeks
Time to additional steroids for asthma
Average change from baseline in Asthma Control Questionnaire (ACQ-5)
Average change from baseline in Asthma Quality of Life Questionnaire; standard version (AQLQ(S))
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time to first severe asthma exacerbation
Time to first moderate or severe asthma exacerbation
Average change from baseline in pre-dose FEV1
Average change from baseline in Morning PEF
Average change from baseline in Evening PEF
Average change from baseline in number of inhalations of ‘as needed’ medication
Average change from baseline in symptom score
Percentage of Nighttime awakenings due to asthma
Percentage of Symptom-free days
Percentage of ‘As needed’ free days
Percentage of Asthma control days
Time to asthma related discontinuation
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 123 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Hungary |
Korea, Republic of |
Mexico |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
South Africa |
Ukraine |
United Kingdom |
Vietnam |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as 'the last visit of the last patient
undergoing the study'. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 8 |